Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.
Rationale: Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug r...
| Publicado en: | Psychopharmacology Vol. 232; no. 21/22; pp. 4191 - 4205 |
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| Autores principales: | , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Nov2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110261408&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110261408 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Nov2015 vid: 232 iid: 21/22 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 110261408 10.1007/s00213-015-4021-z 110261408 ppf: 4191 ppct: 14 formats: fmt: @attributes: type: P tig: atl: Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects. aug: au: Shcherbinin, Sergey Doyle, Orla Zelaya, Fernando Simoni, Sara Mehta, Mitul Schwarz, Adam affil: Tailored Therapeutics - Neuroscience, Eli Lilly and Company, Indianapolis 46285 USA sug: ab: Rationale: Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug response in the presence of another, have not been widely investigated using a task-free ASL approach. Objectives: We assessed the effects of three psychoactive compounds (ketamine, risperidone and lamotrigine), and their interaction, on resting brain perfusion in healthy human volunteers. Methods: A multivariate Gaussian process classification (GPC) and more conventional univariate analyses were applied. The four pre-infusion conditions for each subject comprised risperidone, lamotrigine and two placebo sessions. The two placebo conditions enabled us to evaluate the classification performance in a test-retest setting, in addition to its performance in distinguishing the active oral drugs from placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion scans allowed the effect of ketamine, and its interaction with risperidone and lamotrigine, on brain perfusion to be characterised. Results: The pseudo-continuous ASL measurements of perfusion were sensitive to the effects of ketamine infusion and risperidone. The GPC captured consistent changes in perfusion across the group and contextualised the univariate changes with a larger pattern of regions contributing to accurate discrimination of ketamine from placebo. Conclusions: The findings argue against perfusion changes confounding in the previously described evoked BOLD response to ketamine and emphasise the blockade of the NMDA receptor over neuronal glutamate release in determining the perfusion changes induced by ketamine. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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